Metformin

Not Just For Diabetes.

In the last three years, researchers have shown that diabetic patients with head and neck cancer, may have better outcomes than non-diabetic patients when they are taking the drug metformin for their diabetes. In order to examine this relationship further and understand how metformin changes the biology of cancer cells, researchers at the Sidney Kimmel Cancer Center at Thomas Jefferson University tested tumour cells before and after metformin treatment in non-diabetic cancer patients. The pilot clinical trial results were published in the journal The Laryngoscope.

“This study is the first step in showing how metformin acts on head-and-neck tumours, and we are excited that it could eventually offer patients a method of improving their outcomes with few side effects,” says senior author Ubaldo Martinez-Outschoorn, M.D., Assistant Professor in the Department of Medical Oncology at Thomas Jefferson University and researcher at the Sidney Kimmel Cancer Center.

Dr. Martinez-Outschoorn and colleagues showed that metformin not only changes the pathways that cancer cells rely on to make fuel for growth, but also alters the cancer microenvironment, the cells that surround and support the tumour. “Because tumours need a lot of energy to grow quickly, throwing a wrench in their energy-production pathway makes this kind of cancer more susceptible to standard therapies,” says first author Joseph Curry, M.D., Associate Professor in the Department of Otolaryngology at Jefferson.

The researchers treated 39 patients with metformin and examined their tumour samples before and after metformin treatment. Patients received doses of metformin that were about half of what is given to diabetic patients for a short time-span.

The study looked at molecular markers of cell death, or apoptosis, and changes in metabolic pathways that might make the cancer more susceptible to standard therapy. The patients treated with metformin had a significant increase in tumour cell apoptosis. The cells surrounding the cancer, the so called cancer-supporting fibroblasts, also showed signs of deterioration, indicating that the cells were less capable of helping neighboring cancer cells grow and metastasize to other parts of the body.

Metformin is well-tolerated and has a long track record of being a safe medication, that is much less toxic that traditional cancer treatments. In this study, few patients had side effects from metformin and those that were reported were considered low grade such as gastrointestinal upset. No patients experienced high grade adverse events.

“This study demonstrates that metformin has effects on head-and-neck cancers, at safe doses, that are at or lower than what is given to diabetic patients and that it changes head-and-neck tumour biology in a way that likely makes the cancer easier to kill,” says co-author Madalina Tuluc, M.D., Ph.D., an Associate Professor and Director of Surgical Pathology in the Department of Pathology, Anatomy and Cell Biology at Jefferson. “Metformin disrupts the cancer’s most efficient method of generating fuel for its growth and shuts off the cancer’s support system.” In addition, other work suggests that metformin could have immunotherapeutic effects on tumours as well.

“The next step would be to test these doses of metformin in phase II clinical trials with a greater number of patients,” says Dr. Martinez-Outschoorn.

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Sweet Surprise

A new study is the first of its kind to compare the effects of two types of sugar on metabolic and vascular function. The paper is published in the American Journal of Physiology — Heart and Circulatory Physiology.

Female rats were given a liquid solution of either glucose (a form of sugar found naturally in the body after carbohydrates are broken down) or fructose (sugar found in fruit and fruit juices) in addition to their normal diet of solid food. The rats received the sweetened solutions for eight weeks, roughly equivalent to a person eating large amounts of sugar for six years. The sugar-fed rats were compared with a control group that received plain drinking water in addition to their food supply.

Researchers found that although both sugar-fed groups consumed more calories than the control group, the total calorie intake of the glucose-fed rats was higher than the rats that were given fructose. Another surprising observation was that “despite this difference, only the fructose group exhibited a significant increase in final body weight,” wrote the research team.

In addition to higher weight gain, the fructose group showed more markers of vascular disease and liver damage than the glucose group. These included high triglycerides, increased liver weight, decreased fat burning in the liver (a factor that can contribute to fatty liver) and impaired relaxation of the aorta, which can affect blood pressure.

These findings suggest that an increase in the amount of calories consumed due to sweeteners is not the only factor involved in long-term health risks. The type of sugar may also play a role in increasing risk factors for heart disease, diabetes and other chronic diseases.

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Secret Ingredients

Many herbal supplements contain hidden pharmaceutical ingredients that could be causing serious health risks, according to a team of experts from Queen’s University Belfast, Kingston University London and LGC.

Emeritus Professor Duncan Burns, a forensically experienced analytical chemist from the Queen’s University Belfast’s Institute for Global Food Security, has been working with a team of specialists on a peer-reviewed paper to examine the detection of illegal ingredients in the supplements.

The experts included Dr Michael Walker from the Government Chemist Programme at LGC and Professor Declan Naughton from Kingston University.

The research found that over-the-counter supplements, commonly advertised to treat obesity and erectile dysfunction problems, are labelled as fully herbal but often include potentially dangerous pharmaceutical ingredients, which are not listed on the label.

Professor Burns from Queen’s University, who is working to advance knowledge in this area explained: “Our review looked at research from right across the globe and questioned the purity of herbal food supplements. We have found that these supplements are often not what customers think they are; they are being deceived into thinking they are getting health benefits from a natural product when actually they are taking a hidden drug.

“These products are unlicensed medicines and many people are consuming large quantities without knowing the interactions with other supplements or medicines they may be taking. This is very dangerous and there can be severe side effects.”

The survey raises serious questions about the safety of slimming supplements containing Sibutramine. Sibutramine was licensed as the medicine Reductil until 2010, when it was withdrawn across Europe and the US due to an increased risk of heart attacks and strokes associated with the use of the drug.

Tadalfil and sulfoaildenafil were among the most frequently undeclared ingredients in products for erectile dysfunction. When taken with other medicines containing nitrates, they can lower blood pressure drastically and cause serious health problems.

Professor Burns noted: “This is a real issue as people suffering from conditions like diabetes, hyperlipidemia and hypertension are frequently prescribed nitrate containing medicines. If they are also taking a herbal supplement to treat erectile dysfunction, they could become very ill.

“People who take these products will not be aware they have taken these substances and so when they visit their doctor they may not declare this and it can be difficult to determine what is causing the side effects. It is a very dangerous situation.”

Professor Declan Naughton explained: “This work highlights the vital role research, and in particular, techniques like datamining, can play in informing regulators about current trends in supplement contamination. This is very important to ensure effective testing strategies and, ultimately, to help keep the public safe.”

Dr Michael Walker commented: “The laboratory tests we describe in our paper will assist regulators to tackle this problem proactively to protect consumers and responsible businesses.”

Find the report online here.

 

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Fresh Or Frozen

That Is The Question.

There’s a common belief fresh is best and buying frozen vegies is a cop out.
But certainly on the nutrition front, frozen veg aren’t necessarily inferior, says Melanie McGrice, a spokesperson for the Dietitians Association of Australia.
“Whether fresh is better than frozen, depends on how fresh the vegies actually are,” Ms McGrice said.
“Picking vegies from your own vegie garden out the back has to be the optimal situation. But vegies often have to travel a very long distance to get to us. This can take several days.
“We know that the longer it takes to get fresh food to us from the farm, the more the nutrients in the food slowly decrease.”
On the other hand, the nutrients in frozen produce are sealed into the veg during the freezing process.
One recent British study found antioxidant levels in frozen produce can actually be higher than in fresh fruit and vegetables.
This was “quite surprising”, because people have always thought antioxidant levels would be higher in fresh vegies, Ms McGrice said.
But two independent studies, which together included more than 40 tests on the most commonly bought fruit and vegetables showed in two thirds of cases, frozen foods had higher levels of antioxidant-type compounds, including vitamin C, polyphenols, anthocyanins, lutein and beta carotene on day three of storage.
It’s the water-soluble vitamins including vitamin C and some of the B vitamins that tend to be lost from our fresh produce the longer the vegies hang around, Ms McGrice said.
Vegetables are usually snap frozen very soon after they are picked. Special machinery is used to get the produce to -18 degrees Celsius in minutes.
The nutrients are ‘frozen in’ during this process, meaning you can quite easily have more vitamins in a frozen vegetable than in its ‘fresh’ counterpart.
But there is more to fruit and vegies than just vitamins.
One of the biggest reasons health experts want us to eat fruit and vegies is to get dietary fibre.
The good news is the fibre content doesn’t deteriorate easily, which means week-old fresh vegies still have value despite lowered vitamin levels.
So if it’s a choice of eating old vegetables or no vegies at all, old vegies are fine.
“And freezing doesn’t affect the fibre content of veg,” Ms McGrice adds.
Preparation is key.
How you cook your vegies is far more important than whether they are fresh or frozen.
“Boiling vegies in a large amount of water for a long time lets the vitamins leach out into the water,” Ms McGrice says.
Regardless of whether you are cooking fresh or frozen vegies, use as little water as you can and cook them for a short time. Steaming or microwaving vegies are much better options than boiling.
And if you are using frozen veg, Ms McGrice suggests checking the label of the packet.
“Usually they just contain the vegetable, but sometimes, particularly if there is a sauce, they may contain added salt and sugar,” she says.
(This can be a particular issue if you’re using canned vegetables, which are much more likely to include added salt.)
Here are some points to consider when you’re weighing up the pros and cons of fresh over frozen veg.

Fresh veg.
Can taste better than frozen.
Usually have a better texture.
If you’ve picked them straight from the garden, they will be bursting with nutrients.
But produce can be more than a week old by the time we eat it.
Frozen veg.
Nutrients are ‘frozen in’ soon after picking.
Convenience (can store for months)
Allows us to have vegies and fruit that are out of season
Adds variety to our diet.
After defrosting, vegies can have a soggy texture, because ice crystals damage the vegetable cell walls.

 

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Green Tea

A compound found in green tea could have lifesaving potential for patients with multiple myeloma and amyloidosis, who face often-fatal medical complications associated with bone-marrow disorders, according to a team of engineers at Washington University in St. Louis and their German collaborators.

Jan Bieschke, assistant professor of biomedical engineering at the School of Engineering & Applied Science, studies how proteins fold and shape themselves and how these processes can contribute to a variety of diseases. He says the compound epigallocatechine-3-gallate (EGCG), a polyphenol found in green tea leaves, may be of particular benefit to patients struggling with multiple myeloma and amyloidosis. These patients are susceptible to a frequently fatal condition called light chain amyloidosis, in which parts of the body’s own antibodies become misshapen and can accumulate in various organs, including the heart and kidneys.

“The idea here is twofold: We wanted to better understand how light chain amyloidosis works, and how the green tea compound affects this specific protein,” Bieschke said.

Bieschke’s team first isolated individual light chains from nine patients with bone marrow disorders that caused multiple myeloma or amyloidosis, then ran lab experiments to determine how the green tea compound affected the light chain protein.

Bieschke previously examined EGCG’s effect in both Parkinson’s and Alzheimer’s disease, and found it prevented dangerous buildups of protein present in both diseases. His team had a similar conclusion in this study: In bone marrow patients, the EGCG transformed light chain amyloid, preventing the misshapen form from replicating and accumulating dangerously.

“In the presence of green tea, the chains have a different internal structure,” Bieschke said. “The ECGC pulled the light chain into a different type of aggregate that wasn’t toxic and didn’t form fibril structures,” as happens to organs affected by amyloidosis.

While Bieschke is gaining a greater understanding at the intracellular processes involved, his partners at the University of Heidelberg are working in tandem with him, running clinical trials.

“My group is looking at the mechanism of the protein in a test tube; we are studying how it works on a foundational level. At the same time, clinical trials at the Amyloidosis Center in Heidelberg, with Alzheimer’s in Berlin and with Parkinson’s in China examine the process in people. We all want this compound to work in a patient.”

The research was published in the Journal of Biological Chemistry.

 

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Trucker Health

Commercial truck drivers with three or more medical conditions double to quadruple their chance for being in a crash than healthier drivers, reports a study led by investigators at the University of Utah School of Medicine.

The findings suggest that a trucker’s poor health could be a detriment not only to himself but also to others around him. “What these data are telling us is that with decreasing health comes increased crash risk, including crashes that truck drivers could prevent,” says the study’s lead author Matthew Thiese, Ph.D., an assistant professor at the Rocky Mountain Center for Occupational and Environmental Health (RMCOEH). The results were published in the Journal of Occupational and Environmental Medicine.

Keeping healthy can be tough for truck drivers, who typically sit for long hours behind the wheel, deal with poor sleeping conditions, and have a hard time finding nutritious meals on the road. Now, examination of medical records from 49,464 commercial truck drivers finds evidence that their relatively poor health may put them at risk in more ways than one. 34 percent have signs of at least one of several medical conditions that had previously been linked to poor driving performance, from heart disease, to low back pain, to diabetes.

Matching drivers’ medical and crash histories revealed that drivers with at least three of the flagged conditions were more likely to have been involved in a crash. There were 82 truck drivers in the highest risk group, and results were calculated from millions of data points reflecting their relative crash risk every day for up to seven years. The investigators found that this group was at higher risk for different categories of crashes, including accidents that caused injury, and that could have been avoided.

The rate of crashes resulting in injury among all truck drivers was 29 per 100 million miles traveled. For drivers with three or more ailments, the frequency increased to 93 per 100 million miles traveled, according to Thiese. The trends held true even after taking into consideration other factors that influence truckers driving abilities such as age and amount of commercial driving experience.

The new findings could mean that one health condition, say diabetes, is manageable but diabetes in combination with high blood pressure and anxiety could substantially increase a driver’s risk.

“Right now, conditions are thought of in isolation,” says Thiese. “There’s no guidance for looking at multiple conditions in concert.” Current commercial motor vehicle guidelines pull truckers with major health concerns from the pool but do not factor in an accumulation of multiple minor symptoms.

Considering that occupants of the other vehicle get hurt in three-quarters of injury crashes involving trucks, it’s in the public interest to continue investigating the issue, says the study’s senior author Kurt Hegmann, M.D., M.P.H., director of RMCOEH. “If we can better understand the interplay between driver health and crash risk, then we can better address safety concerns,” he says.

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Aussie Bites

An Australian-first national analysis of 13 years’ data on bites and stings from venomous creatures reveals Australia’s towns and cities are a hot-spot for encounters.

The stereotype-busting research also shows that of all Australia’s venomous creatures, it is bees and other insects, not snakes, spiders, or jellyfish, that pose the biggest public health threat.

Including fatalities, venomous stings and bites resulted in almost 42,000 hospitalisations over the study period. Bees and wasps were responsible for just over one-third (33%) of hospital admissions, followed by spider bites (30%) and snake bites (15%).

Overall, 64 people were killed by a venomous sting or bite, with more than half of these deaths (34) due to an allergic reaction to an insect bite that caused anaphylactic shock.

Snake bites caused 27 deaths. Importantly, snake bite envenoming caused nearly twice as many deaths per hospital admission than other venomous creatures, making snake bite one of the most important venomous injuries to address.

Bees and wasps killed 27 people. Only one case of a beekeeper and one case of a snake catcher was recorded. Tick bites caused three deaths and ant bites another two. And box jellyfish killed three people. There were two unknown insects. No spider bite fatalities were registered.

Public health expert at the Australian Venom Unit at the University of Melbourne, Dr Ronelle Welton, led the study, published in the Internal Medicine Journal. She says she was surprised to find so many deaths and hospitalisations up and down the populated coastal areas of Australia.

“More than half of deaths happened at home, and almost two-thirds (64%) occurred, not in the isolated areas we might expect, but rather in major cities and inner-regional areas where healthcare is readily accessible,” she said.

Researchers believe one of the reasons that anaphylaxis from insect bites and stings has proven deadly may be because people are complacent in seeking medical attention and anaphylaxis can kill quickly.

While three-quarters of snakebite fatalities at least made it to hospital, only 44 per cent of people who died from an allergic reaction to an insect sting got to hospital.

“Perhaps it’s because bees are so innocuous that most people don’t really fear them in the same way they fear snakes,” Dr Welton says. “Without having a previous history of allergy, you might get bitten and although nothing happens the first time, you’ve still developed an allergic sensitivity.”

Western Australia and South Australia were hot spots for stings and bites, and there were no deaths recorded in Tasmania over the decade. Bites and stings were much more likely to occur between April to October.

Dr Welton believes the current national guidelines for prevention and treatment of envenoming is inadequate because we actually know very little about the health burden of venomous creatures.

“From a public health perspective, we can’t make informed decisions until we have a much clearer picture about what’s going on,” she says.

“For example, in South Australia, there are a lot more stings and anaphylaxis from bees. In Queensland there are more snake bites. In Tasmania, their biggest issue is jumper ant anaphylaxis. So the clinical management needs to vary for each state and territory.”

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